RESUMO
The differential gallium-67 (67Ga) accumulation in tumors and inflammatory lesions in rats after i.v. injection of liposome encapsulated 67Ga ([67Ga]liposomes) was studied. The 67Ga accumulation in the tumor was much greater than that in the granulation tissue regardless of the surface charge of liposomes; however, the difference between the two tissues was the greatest when using positive charged liposomes. Gallium-67 delivery to tumors by liposomes was greater than that to granulation tissue in all stages of growth. After i.v. injection, the accumulation of 67Ga in the tumor reached a maximum at 12 hr, whereas in the granulation tissue it was delayed to 24 hr postinjection. In the study of tissue distribution of 67Ga in rats bearing both tumor and granulation tissue, positively charged liposomes preferentially delivered 67Ga to the tumor than to the granulation tissue. These results suggest that [67Ga]liposomes are able to discriminate between the tumor and the inflammatory lesion.
Assuntos
Radioisótopos de Gálio , Inflamação/diagnóstico por imagem , Lipossomos/administração & dosagem , Sarcoma de Yoshida/diagnóstico por imagem , Animais , Carragenina , Colágeno/análise , Diagnóstico Diferencial , Granuloma/diagnóstico por imagem , Granuloma/metabolismo , Inflamação/etiologia , Masculino , Cintilografia , Ratos , Ratos EndogâmicosRESUMO
The in vivo distribution, excretion, and tumor localization of liposome-encapsulated 67Ga in normal and Ehrlich tumor (solid form)-bearing mice were studied. In normal mice, multilamellar vesicles (MLVs) were taken up mainly by the liver and spleen, whereas small unilamellar vesicles (SUVs) exhibited a broader tissue distribution. When 67Ga was encapsulated in MLVs or SUVs, the excretion of the radiotracer in the urine and feces was less than that observed for free tracer at 72 h after i.v. administration. In tumor-bearing mice, SUVs were found to accumulate preferentially in tumors. The tumor uptake of neutral, positive, and negative SUVs was 10%-13% of the administered dose per gram of tumor tissue at 24 h after their injection. These values were about three times higher than those found for free 67Ga-nitrilotriacetic acid (67Ga-NTA) or 67Ga-citrate. Significant differences in tumor uptake due to different surface charges of liposomes were not observed. Enhanced tumor-to-blood and tumor-to-muscle ratios were also observed at 24 h after injection. These results suggest that 67Ga-carrying liposomes may be a useful for tumor imaging.
Assuntos
Carcinoma de Ehrlich/diagnóstico por imagem , Radioisótopos de Gálio , Lipossomos/administração & dosagem , Animais , Masculino , Camundongos , Transplante de Neoplasias , Cintilografia , Distribuição TecidualRESUMO
The effect of cupric acetate on dimethylnitrosamine (DMN)-induced hepatocarcinogenesis in rats was investigated. The surviving rats in the group given DMN (25 ppm) in the drinking water alone were killed at 26 weeks and it was found that 12 of 16 rats had developed liver tumors. In the group given DMN and cupric acetate (sc injections of 2 mg of Cu/kg of body weight once a week for 26 weeks), 7 of 22 rats developed liver tumors. The incidence of liver tumors in rats given DMN and cupric acetate was thus only about 40% of that in rats given DMN alone. No tumor was observed in the group given saline or cupric acetate alone. The thymidine incorporation into the liver DNA of rats was measured at 2 and 4 weeks after the start of the carcinogenicity experiment. The thymidine incorporation into the liver DNA of rats given DMN was significantly suppressed by the administration of cupric acetate. The methylation of liver DNA in rats given a single dose of DMN was also significantly suppressed by sc injection of cupric acetate; the formation of both O6-methylguanine and 7-methylguanine was reduced. This result suggests that sc injection of cupric acetate may have a suppressive effect on the initiation of carcinogenesis in the liver.